| Literature DB >> 9560273 |
J F Barrett1, R M Goldschmidt, L E Lawrence, B Foleno, R Chen, J P Demers, S Johnson, R Kanojia, J Fernandez, J Bernstein, L Licata, A Donetz, S Huang, D J Hlasta, M J Macielag, K Ohemeng, R Frechette, M B Frosco, D H Klaubert, J M Whiteley, L Wang, J A Hoch.
Abstract
A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F two-component signal transduction system in vitro. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase::response regulator two-component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.Entities:
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Year: 1998 PMID： 9560273 PMCID： PMC20258 DOI： 10.1073/pnas.95.9.5317
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205